The minimally invasive technique could lead to advances in mapping the brain and treating neurological disease

A transmitted light image shows the striatum, a region of the mouse brain involved in motor activity planning. The image is overlaid with a colored visualization highlighting cells (in green) that are targeted for neurostimulation. These cells have been infected with a virus that causes them to produce temperature-sensitive ion channels, which can be stimulated remotely via magnetic nanoparticle heating. Credit: Munshi et al, eLife

BUFFALO, N.Y. — Scientists have used magnetism to activate
tiny groups of cells in the brain, inducing bodily movements that
include running, rotating and losing control of the extremities
— an achievement that could lead to advances in studying and
treating neurological disease.

The technique researchers developed is called magneto-thermal
stimulation. It gives neuroscientists a powerful new tool: a
remote, minimally invasive way to trigger activity deep inside the
brain, turning specific cells on and off to study how these changes
affect physiology.

“There is a lot of work being done now to map the neuronal
circuits that control behavior and emotions,” says lead
researcher Arnd Pralle, PhD, an associate professor of physics in
the University at Buffalo College of Arts and Sciences. “How
is the computer of our mind working? The technique we have
developed could aid this effort greatly.”

Understanding how the brain works — how different parts of
the organ communicate with one another and control behavior —
is key to developing therapies for diseases that involve the injury
or malfunction of specific sets of neurons. Traumatic brain
injuries, Parkinson's disease, dystonia and peripheral paralysis
all fall into this category.

The advances reported by Pralle’s team could also aid
scientists seeking to treat ailments such as depression and
epilepsy directly through brain stimulation.

The study, which was done on mice, was published Aug. 15 in
eLife, an open-access, peer-review journal. Pralle’s team
included first authors Rahul Munshi, a UB PhD candidate in physics,
and Shahnaz Qadri, PhD, a UB postdoctoral researcher, along with
researchers from UB, Philipps University of Marburg in Germany and
the Universidad de Santiago de Compostela in Spain.

Magneto-thermal stimulation involves using magnetic
nanoparticles to stimulate neurons outfitted with
temperature-sensitive ion channels. The brain cells fire when the
nanoparticles are heated by an external magnetic field, causing the
channels to open.

Targeting highly specific brain regions

In mice, Pralle’s team succeeded in activating three
distinct regions of the brain to induce specific motor
functions.

Stimulating cells in the motor cortex caused the animals to run,
while stimulating cells in the striatum caused the animals to turn
around. When the scientists activated a deeper region of the brain,
the mice froze, unable to move their extremities.

“Using our method, we can target a very small group of
cells, an area about 100 micrometers across, which is about the
width of a human hair,” Pralle says.

How magneto-thermal stimulation works

“We can target a very small group of cells, an area about 100 micrometers across, which is about the width of a human hair.”

Here's how it works: First, scientists use genetic engineering
to introduce a special strand of DNA into targeted neurons, causing
these cells to produce a heat-activated ion channel. Then,
researchers inject specially crafted magnetic nanoparticles into
the same area of the brain. These nanoparticles latch onto the
surface of the targeted neurons, forming a thin covering like the
skin of an onion.

When an alternating magnetic field is applied to the brain, it
causes the nanoparticles’ magnetization to flip rapidly,
generating heat that warms the targeted cells. This forces the
temperature-sensitive ion channels to open, spurring the neurons to
fire.

The particles the researchers used in the new eLife study
consisted of a cobalt-ferrite core surrounded by a
manganese-ferrite shell.

An advance over other methods, like optogenetics

Pralle has been working to advance magneto-thermal stimulation
for about a decade. He previously demonstrated the
technique’s utility in activating neurons in a petri dish,
and then in controlling the behavior of C. elegans, a tiny
nematode.

Pralle says magneto-thermal stimulation has some benefits over
other methods of deep-brain stimulation.

One of the best-known techniques, optogenetics, uses light
instead of magnetism and heat to activate cells. But optogenetics
typically requires implantation of tiny fiber optic cables in the
brain, whereas magneto-thermal stimulation is done remotely, which
is less invasive, Pralle says. He adds that even after the brains
of mice were stimulated several times, targeted neurons showed no
signs of damage.

The next step in the research is to use magneto-thermal
stimulation to activate — and silence — multiple
regions of the brain at the same time in mice. Pralle is working on
this project with Massachusetts Institute of Technology researcher
Polina Anikeeva, PhD, and Harvard Medical School. The team has $3.5
million in funding from the National Institutes of Health to
conduct continuing studies.

The research published in eLife was funded by the National
Institute of Mental Health and the Human Frontier Science
Program.